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| Name | Class |
|---|---|
| ZonMw: The Netherlands Organisation for Health Research and Development | OTHER |
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This study aims to assess the effectiveness and cost-effectiveness of rectal swab culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal prostate biopsy. Half of participants will receive routine empirical prophylaxis with oral ciprofloxacin (control group), while the other half will receive rectal culture-guided oral antibiotic prophylaxis (intervention group). In the intervention group, men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prophylaxis, comparable to the control group. In case of ciprofloxacin-resistant bacteria an alternative oral antibiotic based on the culture results will be prescribed (trimethoprim/sulfamethoxazole, fosfomycin or pivmecillinam/augmentin).
The investigators hypothesise that the targeted prophylaxis group (intervention group) will have a lower rate of post-biopsy infectious complications compared to the control group.
Several classes of antibiotics are proven effective for prophylaxis during transrectal prostate biopsy, reducing infectious complications to less than 1% in case of susceptible rectal flora. Ciprofloxacin has been best studied and is recommended as first choice prophylaxis in urology guidelines. However, due to increasing fluoroquinolone resistance in gram negative bacilli (currently more than 20% in E.coli), a significant increase up to 6% in infectious complications after transrectal prostate biopsy was recently noticed. Antibiotic treatment of these infections and hospitalization may account for increased health care associated costs and will contribute to the further development of antibiotic resistance.
Besides, in urology guidelines no clear recommendations are made on the duration of prophylaxis. In the Netherlands, therefore, various prophylactic ciprofloxacin schedules are used, of which 2 to 3 day regimens are most common. Prolonged duration of prophylaxis during prostate biopsy is not proven to be more effective than a 1-day regimen, but it is more likely to select more fluoroquinolone (FQ) resistance.
This study aims to assess the effectiveness and cost-effectiveness of rectal culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal prostate biopsy. Also, duration of antibiotic prophylaxis will be minimized to 24 hours, thereby controlling further development of resistant bacteria.
The culture method used in this study with four phenotypic screening agars to support the choice of one of the oral prophylactic antibiotics is innovative. Culture results become available rapidly, within 48 hours, the method is simple, relatively inexpensive, as it does not need full susceptibility testing of separate colonies, and useful in daily practice.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Targeted antimicrobial prophylaxis | Experimental | Men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prior to biopsy (equal to the active comparator arm), and men whose swabs do show ciprofloxacin-resistant bacteria will receive alternative oral antibiotics, based on culture results, in the following order:
|
|
| Routine empirical prophylaxis | Active Comparator | Ciprofloxacin 500 mg orally 2 hours before and 12 hours after transrectal prostate biopsy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ciprofloxacin | Drug | see study arms. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Any registered clinical infectious complication after prostate biopsy | Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis | within 7 days post-biopsy |
| Measure | Description | Time Frame |
|---|---|---|
| Cost of care | Difference of costs between the intervention and the control group | within 30 days after prostate biopsy |
| Positive microbiological results | Urine or blood culture results |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Heiman Wertheim, Prof. dr. | Radboud University Medical Center | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jeroen Bosch Hospital | 's-Hertogenbosch | Netherlands | ||||
| Rijnstate |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37101774 | Derived | Tops SCM, Kolwijck E, Koldewijn EL, Somford DM, Delaere FJM, van Leeuwen MA, Breeuwsma AJ, de Vocht TF, Broos HJHP, Schipper RA, Steffens MG, Wegdam-Blans MCA, de Brauwer E, van den Bijllaardt W, Leenders ACAP, Sedelaar JPM, Wertheim HFL, Adang E. Cost Effectiveness of Rectal Culture-based Antibiotic Prophylaxis in Transrectal Prostate Biopsy: The Results from a Randomized, Nonblinded, Multicenter Trial. Eur Urol Open Sci. 2023 Feb 26;50:70-77. doi: 10.1016/j.euros.2023.02.006. eCollection 2023 Apr. | |
| 36419331 |
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| Trimethoprim/Sulfamethoxazole | Drug | see study arms. |
|
|
| Fosfomycin | Drug | see study arms. |
|
|
| Pivmecillinam/augmentin | Drug | see study arms. |
|
|
| within 7 and 30 days after prostate biopsy |
| Any registered clinical infectious complication after prostate biopsy | Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis | within 7 and 30 days after prostate biopsy |
| Hospitalization after prostate biopsy | Any hospital admission, including ICU admission | within 30 days after prostate biopsy |
| Overall mortality | Mortality of any cause | within 30 days after prostate biopsy |
| Side effects of used antibiotics | All side effects mentioned in the Summary of Product Characteristics (SPC) | within 30 days after prostate biopsy |
| Prevalence of ciprofloxacin-resistant gram negative bacilli in local rectal flora | Assessed through microbiological rectal swab cultures | rectal swabs are taken 14 days before biopsy |
| Overall antibiotic use after prostate biopsy | Number of antibiotic prescriptions | within 30 days after prostate biopsy |
| Arnhem |
| Netherlands |
| Bravis | Bergen op Zoom | Netherlands |
| Amphia Hospital | Breda | Netherlands |
| Catharina Hospital | Eindhoven | Netherlands |
| Zuyderland Hospital | Heerlen | Netherlands |
| Canisius Wilhelmina Hospital | Nijmegen | Netherlands |
| Radboud University Medical Center | Nijmegen | Netherlands |
| Bravis | Roosendaal | Netherlands |
| Zuyderland Hospital | Sittard | Netherlands |
| Elisabeth Tweesteden Hospital | Tilburg | Netherlands |
| Bernhoven Hospital | Uden | Netherlands |
| Isala | Zwolle | Netherlands |
| Derived |
| Tops SCM, Kolwijck E, Koldewijn EL, Somford DM, Delaere FJM, van Leeuwen MA, Breeuwsma AJ, de Vocht TF, Broos HJHP, Schipper RA, Steffens MG, Teerenstra S, Wegdam-Blans MCA, de Brauwer E, van den Bijllaardt W, Leenders ACAP, Sedelaar JPM, Wertheim HFL. Rectal Culture-Based Versus Empirical Antibiotic Prophylaxis to Prevent Infectious Complications in Men Undergoing Transrectal Prostate Biopsy: A Randomized, Nonblinded Multicenter Trial. Clin Infect Dis. 2023 Apr 3;76(7):1188-1196. doi: 10.1093/cid/ciac913. |
| ID | Term |
|---|---|
| D007239 | Infections |
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D002939 | Ciprofloxacin |
| D015662 | Trimethoprim, Sulfamethoxazole Drug Combination |
| D005578 | Fosfomycin |
| D000561 | Amdinocillin Pivoxil |
| D019980 | Amoxicillin-Potassium Clavulanate Combination |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D013420 | Sulfamethoxazole |
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D014295 | Trimethoprim |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D000560 | Amdinocillin |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D019818 | Clavulanic Acid |
| D002969 | Clavulanic Acids |
| D000658 | Amoxicillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
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